tbuckley/cabot-search huggingface dataset:
Bendamustine-bortezomib-dexamethasone in relapsed/refractory multiple myeloma.
Authors: Claudio Cerchione, Davide Nappi, Delia Cangini, Sonia Ronconi, Michela Ceccolini, Gerardo Musuraca, Giovanni Martinelli
Journal: Journal of Clinical Oncology (2023)

e20051 Background: Bendamustine is an old bi-functional alkylating agent which has proved to be effective in relapsed, refractory and in new diagnosed Multiple Myeloma (MM). Thus, aiming to provide further insights in this field, also in novel agents’era, we present here a retrospective, real-life analysis of patients with relapsed/refractory MM (rrMM), who had received salvage therapy with bendamustine in combination with bortezomib and dexamethasone (BVD). Methods: 81 patients (44 M/37 F), with rrMM, median age at diagnosis 59.4 years (r. 36-82), median age at start of treatment 63.6 years (r.37-86) treated with several lines of treatments (median 6, r. 2-11), every refractory to all the drugs previously received (also Bortezomib), received BVD (B 90 mg/sqm days 1,2; V 1.3 mg/sqm days 1,4,8,11, D 20 mg days 1,2,4,5,8,9,11,12, Pegfilgrastim day +4) every 28 days, until progression. Setting and Patients: All patients had previously received bortezomib-based and IMIDs-based treatments, and 32% (26/81) had also received radiotherapy. 69% (56/81) had undergone single or double autologous and three (2%) allogeneic stem cell transplant. Results: Bendamustine was well tolerated, with grade 3-4 transfusion-dependent anemia in 56% (46/81) of patients, and 43% (35/81) grade 3-4 neutropenia (no ospedalization was required, no septic shocks were observed). No severe extrahematologic toxicity was observed, only grade 1 gastrointestinal side effect (nausea), treated by common antiemetic drugs. ORR was 63% (51/81: 7 CR, 18 VGPR, 15 PR, 11 MR) with 11 PD and 19 patients in SD, impressive result in this subset of rrMM patients. In particular, for 11 patients, BVD was, after having achieved at least a PR, a bridge to second auSCT, and for two patients a bridge to alloSCT. Eight patients have surprisingly achieved a notable PR after failure of novel agents (i.e. Carfilzomib, Daratumumab and Pomalidomide). Median time to response was 1.3 months (r.1-3), median OS from diagnosis was 67.3 months (r.6-151), median OS from start of Bendamustine was 9.6 months (r.2-36). Conclusions: BVD has shown significant efficacy in a particularly severe setting of patients, relapsed and refractory to all available therapeutic resources, and, in particular cases, it could be considered as a bridge to SCT, also after failure of novel agents. Clinical trial information: FEDII 2022000378 .
Prognostic significance of pseudoprogression defined with lowered threshold iRECIST criteria in advanced melanoma treated with immune checkpoint inhibitor therapy.
Authors: Joseph S. Park, Milos Josef Janicek, Adam Lerner
Journal: Journal of Clinical Oncology (2023)

e21536 Background: The advent of immune checkpoint inhibitor (ICI) therapy has dramatically improved survival in advanced melanoma. Unique to ICI therapy, pseudoprogression (PP) is characterized by an initial radiographic increase in tumor size followed by shrinkage. Modifications to RECIST have been proposed in order to better distinguish this phenomenon from progressive disease (PD). In iRECIST, a &gt; 20% initial increase in target lesions is required to define PD or PP. Here, we assessed whether lowering this threshold would enhance identification and prognostication of pseudoprogression. Methods: In this single-center retrospective cohort study, we analyzed 37 patients with stage IV melanoma treated with PD-1 or CTLA inhibitors. The outcome was overall survival. Imaging from the staging, 1st and 2nd restaging scans were blindly assessed by a radiologist and assigned summed scores of primary tumor and up to 5 metastases. In lowered threshold iRECIST (LT-iRECIST), PP was defined as score increase &gt; 5% on 1st restaging followed by decrease &lt; -5% on 2nd restaging. PD was defined as score increase &gt; 5% on both 1st and 2nd restaging. Regression was defined as score decrease &lt; -5% on both 1st and 2nd restaging. Survival odds and hazard ratios were calculated with univariate Cox regression. The analysis was repeated with the threshold set to ±20% (traditional iRECIST). Results: In the overall cohort, median survival was 861 days. Median time to 1st and 2nd restaging scans was 112 days and 214 days respectively. 5 patients (13.5%) met criteria for PP with traditional iRECIST compared to 9 (24.3%) with LT-iRECIST. Two-year survival odds for PD, PP and regression were 20%, 80% and 66.7% respectively with traditional iRECIST, and 12.5%, 88.9% and 58.3% with LT-iRECIST. Hazard ratios for PP and regression were 0.329 (p &gt; 0.1) and 0.296 (p &gt; 0.1) respectively with traditional iRECIST, and 0.111 (p &lt; 0.01) and 0.269 (p &lt; 0.05) with LT-iRECIST. Conclusions: Harnessing the first two restaging scans and lowering the threshold from 20% to 5% in iRECIST led to identification of a group of patients in whom pseudoprogression is associated with a significant survival benefit. In advanced melanoma treated with ICI, adopting this iRECIST modification may allow early discrimination of pseudoprogression and its associated favorable outcome. [Table: see text]
Non-hematopoietic cell transplant-related veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) in solid tumor and hematologic malignancies: A systematic review.
Authors: Fiona Stewart, Kimberly Ruiz, Malia Gill, Darsh Devani, Nicole Fusco, Lin Fan, Vian Amber, Raj Hanvesakul, Alexandra Gangi
Journal: Journal of Clinical Oncology (2023)

e24094 Background: VOD/SOS is a serious liver injury caused by toxic damage to sinusoidal endothelial cells. It has been linked to conditioning regimens preceding hematopoietic cell transplant (HCT) but little is known about its epidemiology and characteristics outside the HCT setting. We conducted a systematic review to examine the incidence, burden of illness, and management of non-HCT VOD/SOS. Methods: We searched MEDLINE, Embase (2002–2022), and relevant congress proceedings (2019–2022) for studies reporting incidence, diagnosis, clinical and patient characteristics, humanistic and economic burden, and treatments in non-HCT VOD/SOS. All study designs were eligible except case series of &lt; 5 patients. Pyrrolizidine alkaloid-induced VOD/SOS was excluded. Results: We identified 3,544 records and included 80 studies; 58% were retrospective cohort studies. Sample sizes ranged from 5 to 12,941; 38% of the studies included &gt; 100 patients. The highest incidences of non-HCT VOD/SOS were in patients with colorectal liver metastases (CLM) (median 41%) and Wilms tumor (median 14%) (table). Diagnostic criteria were heterogenous. Rubbia-Brandt histological criteria were used in CLM. In other disease settings, diagnosis varied and was based on clinical criteria (eg, McDonald, Seattle, or Baltimore). Management of VOD/SOS included defibrotide, supportive therapy (eg, fluid restriction, blood products) and switching/pausing chemotherapy. No usable data were found on humanistic/economic burden. Conclusions: Non-HCT VOD/SOS occurs in diverse disease areas, including hematologic and solid tumor cancers. Lack of consensus regarding diagnosis of non-HCT VOD/SOS may indicate underdiagnosis. Clinicians should be vigilant for VOD/SOS even in non-HCT patients. Defibrotide is approved for post-HCT VOD/SOS but there is no approved therapy for non-HCT VOD/SOS; future trials should focus on diagnosis and treatment outside the HCT setting, which represents a significant unmet need. A limitation of the current work is the suboptimal reporting and low methodological quality in some primary studies.[Table: see text]
Clinical outcomes of patients with multiple myeloma following disease progression after BCMA-targeted CAR T-cell therapy.
Authors: Naveen G. Subramanian, Hector Garcia Pleitez, Oren Pasvolsky, Nilesh Kalariya, Krina K. Patel, Christopher J. Ferreri
Journal: Journal of Clinical Oncology (2023)

e20002 Background: While BCMA-targeted CAR T therapies have yielded unprecedented efficacy in patients with multiple myeloma, most patients (pts) experience disease relapse. Treatment after progression on CAR T has become an unmet need given the limited novel treatment options available. We evaluated clinical outcomes for pts relapsing after BCMA CAR T. Methods: This was a single-center retrospective analysis including pts who had been treated with a BCMA-targeted CAR T therapy prior to 12/31/22 and then had disease progression. Data for all subsequent lines of therapy were collected, and best response to therapy was graded as per IMWG criteria. Statistics were descriptive in nature. Results: Thirty pts treated with BCMA CAR T (14 trial, 16 commercial) relapsed. The cohort of median age 61 had notable disease characteristics of 40% with high-risk FISH and 30% with extramedullary disease (EMD). The median number of prior lines of therapy (LOT) was 5, with 80% triple-class refractory and 47% penta-refractory. Patients treated with late BCMA CAR T (≥ 4 prior LOT; n=20) had higher rates of EMD (40% v 10%), triple-class refractory (90% v 60%), and penta-refractory disease (55% v 30%) compared to pts who received early CAR T (&lt; 4 prior LOT; n=10). At data cutoff, 4 pts died without receiving subsequent therapy and 1 pt was pending start of their first regimen. The remaining 25 pts received 58 salvage therapies, of which 54 regimens were evaluable for response. The overall response rate (ORR) for all regimens was 46%. Median overall survival (OS) was not reached, and the 6 and 12-month OS rates were 83% and 77% respectively. ORR and median progression free survival (PFS) stratified by the specific type of salvage therapy are shown in the table. Patients who received a regimen consisting only of agents they had received in a prior LOT had an ORR of 57% and median PFS of 3.6 months. Patients who received early CAR T had a higher ORR to all subsequent salvage therapies (59% v 33%), longer median PFS (4.6 months v 1.6 months), and higher 12-month OS (90% v 70%). Conclusions: For pts with progression after BCMA CAR T, treatment with another BCMA CAR T or transplant had more favorable outcomes. Retreatment with prior therapies resulted in disease control for a fair number of patients, which can serve as a bridge to another novel therapy. The pts treated with early CAR T had more favorable post-progression outcomes than late CAR T, yet 70% of pts who received late CAR T were alive at 1 year post-progression. [Table: see text]
Comparison of outcomes of <i>Clostridium difficile</i> infection in autologous stem cell transplant recipients compared to allogenic stem cell transplant recipients.
Authors: Kanwal Bains, Armaan Dhaliwal, Aalam Sohal, Hunza Chaudhry, Ishandeep Singh, Dino Dukovic, Kirti Arora, Shivam Kalra, Ponnandai Sadasivan Somasundar
Journal: Journal of Clinical Oncology (2023)

e19064 Background: Hematopoietic stem cell transplant (HSCT) recipients are at a higher risk of clostridium difficile infection (CDI). The incidence of CDI in allogenic SCT recipients has been shown to be about 2-fold compared to autologous SCT recipients in certain studies. These differences can be attributed to myeloablative chemotherapy and increased duration of immunosuppression in allogenic SCT patients. In this study we evaluate the impact of CDI on in-hospital outcomes in these two groups of patients. Methods: We included all patients with a prior diagnosis or a procedure code for HSCT and CDI using ICD-10 codes from National Inpatient Sample 2016-2019. Patients were stratified into two groups based on the presence or absence of autologous stem cell transfusion. Information was collected regarding patient demographics, Charlson comorbidities, resource utilization (LOS and total hospitalization charges), and outcomes. The outcomes included sepsis, shock, acute kidney injury, ICU admission, and in-hospital mortality. The differences in outcomes between the two groups were studied. Results: The incidence of CDI in autologous stem cell transplant recipients was lower compared to the allogenic HSCT group (5.1% vs. 6.1%, p-0.003). 7,605 patients were included in the study. Of them, 2,460 (32.25%) patients had autologous stem cell transplantation, while the remaining had allogenic stem cell transfusion. A higher proportion of patients in the autologous stem cell transplant group were males (60.7% vs. 54.32%), and patients aged 45-64 years (55.7% vs. 46.4%). Patients who received autologous stem cell transplants had a lower incidence of death (1.6% vs. 7.8%, p &lt; 0.001), sepsis (17.28% vs. 28.18%, p- &lt; 0.001), shock (4.7% vs. 12%, p &lt; 0.001), AKI (15% vs. 31.6%, p &lt; 0.001) and ICU admissions (5.7% vs. 10.7%, p- &lt; 0.001). There was no significant difference in the length of stay between the two groups (21.30 days vs 22.97 days). Patients in the autologous stem cell transplant group had lower hospitalization charges ($318,072.3 vs $402,281.5, p &lt; 0.001) than the allogenic group. Conclusions: Like prior studies, our study is compatible with the lower incidence of CDI in autologous SCT recipients. Our study also suggested a lower in-hospital mortality and better outcomes compared to patients with allogeneic stem cell transplants. Resource utilization was also noted to be lower in autologous stem cell transplant patients. Further research should be conducted to explain the differences and to allow physicians to provide timely treatments to prevent worse outcomes.
Protective effect of the dexrazoxane against cardiotoxicity of the anthracycline in the treatment of the childhood cancers.
Authors: Nurdan Tacyildiz, Nazmiye Turker, Tayfun Ucar, Sonay Incesoy Ozdemir, Handan Dincaslan, Melek Yaman Ortakoylu, Mehmet Gokhan Ramoglu, Gulsan Yavuz, Emel Cabi Unal
Journal: Journal of Clinical Oncology (2023)

e22001 Background: Cardiovascular diseases have become the most important cause of morbidity and mortality in the long-term follow-up of childhood cancer survivors. Dexrazoxane (DEX) is the only FDA-approved drug to prevent Anthracycline-induced cardiotoxicity. In this study, we aimed to evaluate the cardioprotective efficacy of DEX in patients using Anthracycline in the treatment of childhood cancer. Methods: 142 patients aged 0-18 years, who were treated with cancer diagnosis in Ankara University Faculty of Medicine, Department of Pediatrics, Department of Pediatric Oncology, and who had been treated with Anthracycline group agents, were evaluated retrospectively. The cardiac functions of 87 patients who received only Anthracycline between November 2009 and March 2019 and 55 patients who received DEX + Anthracycline between March 2019 and June 2021 were compared. An ejection fraction (EF) of less than 50% in cardiac evaluation was defined as 'cardiac dysfunction'. Results: The group that received anthracycline with DEX; While 50.9% were girls, 49.1% were boys, and the mean age was 98.42 months, 48.3% of the group that took only Anthracycline was girls and 51.7% were boys, with a mean age of 105.75 months. There was no difference between the two groups in terms of diagnosis distribution. EF values of both groups before anthracycline were normal. While none of the patients in the DEX + Anthracycline group developed cardiac dysfunction during the follow-up, 11 (12.6%) patients in the Anthracycline group with no DEX had cardiac problems. Six Of the 11 patients (54.5%) who developed cardiac dysfunction died(p=0.012). There was a significant difference between the two groups with or without DEX patients in the manner of cardiac dysfunction(p=0.006) and death(p=0.009). Cardiac dysfunction development and mortality rates were higher in patients using only Anthracycline. Conclusions: In this study, it has been shown that DEX is very effective for preventing Anthracycline-related cardiac dysfunction, which is one of the most important causes of mortality and morbidity in childhood cancer survivors.
Phase 1 trial of avelumab with hypofractionated thoracic radiation therapy (HT-RT) in patients with metastatic soft-tissue sarcomas (mSTS).
Authors: Shane H Zaidi, Nicos Fotiadis, Yolanda Augustin, Andrea Napolitano, Caitriona Goggin, Bernice Asare, Elizabeth Barquin, Steven Edmunds, Khin Thway, Charlotte Benson, Robin L Jones, Aisha B Miah
Journal: Journal of Clinical Oncology (2023)

11552 Background: Combining HT-RT with anti PD-L1 therapy may enhance local and distant tumour control in mSTS. This was a Phase 1 trial to evaluate the safety, tolerability, and efficacy of avelumab in patients with mSTS. Methods: This was a single centre phase 1 trial of avelumab with HT- RT in patients with mSTS (NCT03602833). Patients &gt; 18 years with at least 2 pulmonary metastases, ECOG performance status 0-1 were eligible between Oct 2018-Apr 22. Patients received HT-RT (36 Gy in 12 fractions), with concurrent intravenous avelumab (10 mg/kg q14d) until disease progression. The primary end point was safety of avelumab with HT-RT. Secondary endpoints included local control rate at 3 months. Dose limiting Toxicity (DLT) assessed from start of HR-CT and avelumab up to Cycle 7 avelumab and defined as: ≥ G2 pneumonitis, ≥ G2 myelitis, ≥ G3 non-haem toxicity, ≥ any other G4 and/or HT-RT interruption &gt; 5 days. Response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST). Results: 12 patients were treated in this trial. Histological subtypes: leiomyosarcoma (n = 2), undifferentiated pleomorphic sarcoma (n = 2), and spindle cell sarcoma (n = 2). The median age was 57.5 (37-68) years, 7 were female (58%). All patients had lung metastases. 1 previously received SBRT to the lung, and 5 (42%) patients had received prior systemic treatment. 12 patients received at least one cycle of avelumab, median 9 (range: 1-37), and treatment was discontinued in 11 (92%) patients; 10 (83%) stopping for progressive disease, 1 (8%) patient for G4 immune-mediated hepatitis after DLT period and 1 patient completed and continues on compassionate-use avelumab. Eleven (92%) completed radiotherapy (36 Gy, 12 fractions). No DLTs or treatment-related deaths were observed. HT-RT toxicity: 3 G2 acute (1 oesophagitis, 2 skin) noted up to 11 weeks. 13 G1 late toxicities (5 pneumonitis, 5 skin, 1 cardiac, 1 myelitis, 1 oesophagitis) reported. Avelumab toxicities: 2 G3 (1 ALT rise, 1 viral infection) and 3 G4 (1 AST rise, 1 hepatitis, 1 sepsis) reported after DLT observation period. The median follow-up was 21.8 (range 3.2-31.9) months with a 3-month local control rate of 50% (95% CI, 21%-74%). RECIST responses at 3 months were 0 CR, 1 (8%) PR, 5 (42%) SD and 5 (42%) PD. Conclusions: Avelumab in combination with thoracic radiotherapy was safe with encouraging anti-tumour activity in patients with metastatic soft-tissue sarcomas. Additional molecular biomarker analyses are in progress. Clinical trial information: NCT03602833 .
Incorporation of fellow-driven, interactive case-based discussions to improve fellowship education in a new fellowship program.
Authors: Arthi Sridhar, Sama Imran Ilyas, Julie H Rowe, Neha Maithel
Journal: Journal of Clinical Oncology (2023)

e23001 Background: Evidence-based education is crucial for meeting the evolving needs of learners in the oncology workforce. In this new virtual era, engagement of trainees in educational presentations has become increasingly difficult and reaping the benefits of a conventional didactic learning environment is challenging. Case-based learning is a relatively newer modality that is being used more commonly in teaching programs. In this study, we aimed to incorporate a novel, interactive case-based learning paradigm to improve fundamental knowledge and engagement among oncology trainees. Methods: We conducted six case conferences over 6 months. The case conferences were designed to encourage open discussion of real-life oncology cases. A faculty expert and specific topics were assigned to the presenters: colon, breast, gastric, hepatocellular (HCC), prostate, and non-small cell lung (NSCLC) cancer. Guidelines on the preparation of the case presentation were provided with 5 main pillars: specific staging/workup, first-line management with a landmark trial, second-line management, case-specific challenges, and mechanism of action and monitoring parameters for discussed drugs. Fellows completed a pre- and post-conference survey that assessed their perceived comfort level with the topic, quality of the presentation (post-conference) utilizing the 1–5 Likert scale (5 being extremely satisfied/comfortable), and test questions. Results: Nearly all of the 6 fellows responded to all surveys. The table shows the mean scores given by fellows on the surveys using the Likert scale and the percentage of test questions answered correctly. Overall, the fellows felt that the case conferences were a worthwhile experience. When comparing pre- and post-conference questions, the percentage of test questions correct overall improved for 5 of 6 conferences. Conclusions: The results of our study could have implications for the curriculum planning of hematology/oncology fellowships. [Table: see text]
Symptom burdens in long-term survivors of gynecologic cancer receiving acupuncture care.
Authors: Christopher K. Daugherty, Kathleen J. Hanold, Fay J. Hlubocky
Journal: Journal of Clinical Oncology (2023)

e24152 Background: Gynecologic cancer survivors (GCS) experience physical and emotional symptom burdens (SB) due to advanced, recurrent disease and intensive treatment often requiring supportive, complementary/integrative therapies. Yet, limited evidence exists on which specific SB require attention and intervention. This study aimed to identify demographics and SB of GCS referred for outpatient acupuncture services at a U.S. cancer center. Methods: A retrospective analysis was conducted of GCS actively receiving outpatient acupuncture services at the University of Chicago Supportive Oncology Program between March 2021 and June 2022. A brief self-reported SB assessment using a 0-10 Likert rating scale was completed at each acupuncture treatment. Socio-demographic (age, religion), disease information (stage) and SB (pain, insomnia) information was obtained from the medical record. Descriptive statistics were analyzed and paired sample t-tests evaluated SB differences prior to first and final treatment. Results: Eighty-three percent (54 of 65 referred) GCS received outpatient acupuncture care. Seventeen percent (11 of 65 referred) were unable to seek acupuncture due to disease progression leading to referral for end-of-life care (e.g. hospice, home palliative care). The mean age of GCS receiving acupuncture was 60y (range 30-81); 97% Non Hispanic, 65% White; 32% African American; 58% married; 53% with children; 65% Christian; 59% retired/on disability. Fifty percent of GCS had endometrial dx, 47% ovarian; 95% Stage IV; mean 7y since dx (range = .6-20y); 88% lacked advanced directives (e.g. DNR). Seventy percent completed at least four weekly acupuncture treatments. Prevalent SB were fatigue (94.1%), sleep disturbance (88.3%), pain (88.2%), anxiety (82.6%); and neuropathy (52.9%). On average, elevated SB mean scores were fatigue, numbness, anxiety, and hot flashes. Neuropathy was scored as the most severe (≥8 of 10). No significant improvement in SB was identified at the third treatment (p = 0.10). At the sixth session, GCS reported significantly less pain (p = 0.02). SB change was both statistically and clinically significant in 61-73% GCS at last session, except nausea. Only 0-5% of GCS reported worsening SB after acupuncture. Conclusions: Our results suggest acupuncture may aid in GCS SB control serving as a useful adjunct during cancer treatment and beyond. Early acupuncture referral may benefit GCS coping with SB during the cancer trajectory and is warranted. Future research should use a longitudinal prospective cohort design with validated SB measures.